Hair regrowth in alopecia areata and re-pigmentation in vitiligo in response to treatment: Commonalities and differences

Abstract

Both alopecia areata (AA) and vitiligo share common pathogenesis involving, interferon-γ (IFN-γ) and interleukin-15 (IL-15) signalling pathways that activate cytotoxic CD8+ T lymphocytes. These shared mechanisms may explain why both diseases respond to currently available treatments (e.g. topical/systemic corticosteroid) and emerging treatment modalities. As compared with the speed of re-pigmentation in vitiligo lesions, the regeneration of pigmented terminal hair follicles in AA lesions appears fast in response to treatments targeting the inhibition of the Janus kinases (JAKs) and other kinases. We summarize the commonalities and differences between AA and vitiligo focusing on the treatment modalities, followed by recent findings associated with hair follicle stem cells (HFSC) in hair bulge (HBg) and melanocyte stem cells (McSC) in HBg and hair germ (HGm). We then discuss how HFSC and HGm-McSC are involved in the initiation of anagen phase, followed by pigmented terminal hair regrowth in the recovering AA lesions in association with immunology. We also discuss how HBg-McSC contribute to the migration of fully dendritic mature melanocytes into interfollicular epidermis and the equal distribution of melanin in recovering vitiligo lesions. Finally, we present four hypotheses to elucidate the delayed distribution of melanin by mature melanocytes in depigmented vitiligo lesions from the aspects of stem cell biology, as compared with quick hair recovery in AA: (1) McSC are less abundant than HFSC. (2) McSC require a long travel, whereas HFSC reside close to hair regeneration trigger point. (3) Keratinocyte scaffold to accept melanin is not well preserved, whereas scaffold for hair regrowth is well preserved. (4) Inhibitors targeting JAKs and other kinases have less direct effects on melanocyte proliferation and differentiation in vitiligo than hair regrowth in AA. Our review provides an overview of treatment modalities and bridges the gap between scientific advancement and clinical practice in AA and vitiligo management.